Role of Cell Motility in the Activity of Cytolytic T Lymphocytes

  • J.-E. Ryser
  • P. Vassalli
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 146)


The distinction between specific recognition and target cell (TC) lysis has been accepted as a useful concept in the analysis of cytolytic T lymphocyte (CTL)-mediated cytotoxicity. Recently, this process has been resolved by different methods into three steps: binding; “lethal hit”; and TC lysis; the first two of which require direct CTL-TC contact (1,2). As detailed in recent reviews (3–7), CTL-TC conjugates can be isolated physically before the lethal hit step (2,8–10), or binding and lethal hit can be separated on the basis of different cations requirements (11,12), and different susceptibilities to inhibition by low temperature (15®C) and drugs (3). These different sensitivities to temperature, extracellular cations and pharmacological compounds could mean that qualitatively different intracellular activities and/or membrane-associated phenomena operate in the binding and lethal hit steps.


Conjugate Formation Specific Target Cell Binding Step Binding Area Cell Mediate Cytolysis 


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  1. 1.
    Martz, E., and B. Benacerraf. An effector-cell independent step in target cell lysis by sensitized mouse lymphocytes. J. Immunol. 111:1538 (1973).PubMedGoogle Scholar
  2. 2.
    Martz, E. Early steps in specific tumor cell lysis by sensitized mouse T-l3miphocytes. I. Resolution and characterization. J. Immunol. 115:261 (1975).PubMedGoogle Scholar
  3. 3.
    Cerottini J.-C., and K.T. Brunner. Mechanisms of T and K cell- mediated cytolysis. In F. Loor and G.E. Roselants, B and T cells in immune recognition, p. 319, Wiley and Sons, Chichester, England (1977).Google Scholar
  4. 4.
    Golstein, P., and E.T. Smith. Mechanism of T-cell-mediated cytolysis: the lethal hit stage. Contemp. Top. Immunobiol. 7:273, Plenum Press, New York (1977).PubMedCrossRefGoogle Scholar
  5. 5.
    Henney, C.S. T-cell-mediated cytolysis: an overview of some current issues. Contemp. Top. Lnmubiol. 7:245, Plenum Press, New York (1977).CrossRefGoogle Scholar
  6. 6.
    Martz, E. Mechanism of specific tunnor-cell lysis by alloimmune T lymphocytes: resolution and characterization of discrete steps in the cellular interaction. Contemp. Top, Immunobiol 7:301, Plenum Press, New York (1977).CrossRefGoogle Scholar
  7. 7.
    Berke, G. Interaction of cytotoxic T lymphocytes and target cells. Prog. Allergy 27:69 (1980).PubMedGoogle Scholar
  8. 8.
    Zagury, D., Bernard, J., Thiernesse, N., Feldman, M., and G. Berke. Isolation and characterization of individual functionally reactive cytotoxic T lymphocytes: conjugation, killing and recycling at the single cell level. Eur. J. Immunol. 5:818 (1975).CrossRefGoogle Scholar
  9. 9.
    Sanderson, C.S. The mechanisms of T cell mediated cytotoxicity. II. fforphological studies on cell death by time-lapse microcinematography. Proc. Roy. Soc. Lond., Ser. B 192:241 (1976).Google Scholar
  10. 10.
    Ryser, J.-E., Sordat, B., Cerottini, J.-C., and K.T. Brunner. Mechanism of target lysis by cytotoxic T lymphocytes. I. Characterization of specific lymphocyte-target cell conjugates separated by velocity sedimentation. Eur. J. Immunol. 7:110 (1977).PubMedCrossRefGoogle Scholar
  11. 11.
    Golstein, P., and E.T. Smith. The lethal hit stage of mouse T and non-T cell mediated cytolysis: differences in cation requirements and characterization of an analytical “cation pulse” method. Eur. J. Immunol. 6:81 (1976).CrossRefGoogle Scholar
  12. 12.
    Plaut, M., Bubbers, J.E., and C.S. Henney. Studies on the mechanism of lymphocyte-mediated cytolysis. VII. Two stages in the T cell-mediated lytic cycle with distinct cation requirements. J. Immunol. 116:150 (1976).PubMedGoogle Scholar
  13. 13.
    Golstein, P. Sensitivity of cytotoxic T cells to T cell- mediated cytotoxicity. Nature 252:81 (1974).PubMedCrossRefGoogle Scholar
  14. 14.
    Küppers, R.C., and C.S. Henney. Evidence for direct linkage between antigen recognition and lytic expression in effector T cells. J. Exp. Med. 143:684 (1976).PubMedCrossRefGoogle Scholar
  15. 15.
    Küppers, R.C. and C.S. Henney. Studies on the mechanism of lymphocyte-mediated cytolysis. IX. Relationships between antigen recognition and lytic expression in killer T cells. J. Immunol. 118:71 (1977).PubMedGoogle Scholar
  16. 16.
    Sanderson, C.J. The Machanism of lymphocyte-mediated cytotoxicity. Biol. Rev. 56:153 (1981).PubMedCrossRefGoogle Scholar
  17. 17.
    Sanderson, C.J. The mechanism of T cell mediated cytotoxicity. VIII. Zeiosis corresponds to irreversible phase (programming for lysis) in steps leading to lysis. Immunology 42:201 (1981).PubMedGoogle Scholar
  18. 18.
    Koren, H.S., Ax, W., and E. Freund-Moelbert. MDrpholpgical observations on the contact-induced lyis of target cells. Eur. J. Immunol. 3:32 (1973).PubMedCrossRefGoogle Scholar
  19. 19.
    Matter, A. Microcinematographic and electron microscopic analysis of target cell lysis induced by cytotoxic T lymphocytes. Immunology 36:179 (1979).PubMedGoogle Scholar
  20. 20.
    Chang, T.W., Celis, E., Eisen, H.N., and F. Salomon. Crawling movements of lymphocytes on and beneath fibroblasts in culture. Proc. Natl. Acad. Sci. USA 76:2917 (1979).PubMedCrossRefGoogle Scholar
  21. 21.
    Grimm, E., Price, Z., and B. Bonavida. Studies on the induction and expression of T cell-mediated immunity. VIII. Effector-target junctions and target cell membrane disruption during cytolysis. Cell. Immunol. 46:77 (1979).PubMedCrossRefGoogle Scholar
  22. 22.
    Matter, A., and P. Vassalli. Ultrastructure and fuctional study of cytotoxic T lymphocytes. G. Raspe, Advances in the biosciences 12, p. 57, Pergamon Press, Vieweg (1973).Google Scholar
  23. 23.
    Chang, T.W., and H.N. Eisen. Lymphomas with cytotoxic activity. nature 280:406 (1979).Google Scholar
  24. 24.
    Rothstein, T.L., Mage, M., Jones, G., and L.L. McHugh. Cytotoxic T lymphocyte sequential killing of immobilized allogenic tumor target cells measured by time-lapse microcinematography. J. Immunol. 121:1652 (1978).PubMedGoogle Scholar
  25. 25.
    Berke, G., Sullivan, K.A., Amos, D.B. Tumor immunity in vitro: destruction of a mouse ascites tumor through a cycling pathway. Science 177:433 (1972).PubMedCrossRefGoogle Scholar
  26. 26.
    Cerottini, J.-C., and K.T. Brunner. Reversible inhibition of lymphocyte-mediated cytotoxicity by cytochalasin B. Nature (New Biol.) 237:272 (1972).Google Scholar
  27. 27.
    Plaut, M., Lichtenstein, L.M., and C.S. Henney. Studies on the mechanism of lympocyte-mediated cytolysis. III. The role of microfilaments and microtubules. J. Immunol. 110:771 (1973).PubMedGoogle Scholar
  28. 28.
    Liepins, A., Foanes, R.B., Lifter, J., Choi, Y.S., and E. de Harven. Ultrastructural changes during T-lymphocyte-mediated cytolysis. Cell. Immunol. 28:109 (1977).PubMedCrossRefGoogle Scholar
  29. 29.
    Berke, G., Gabison, D., and M. Feldman. The frequency of effector cells in populations containing cytotoxic T lymphocytes. Eur. J. Immunol. 5:813 (1975).CrossRefGoogle Scholar
  30. 30.
    MacDonald, H.R. Early detection of potentially lethal events in T cell mediated cytolysis. Eur. J. Immunol. 5:251 (1975).PubMedCrossRefGoogle Scholar
  31. 31.
    Grimm, E.A., and B. Bonavida. Studies on the induction and expression of T-cell mediated immunity. VI. Heterogeneity of lytic efficiency exhibited by isolated cytotoxic T lymphocytes prepared from hghly enriched populations of effector-target conjugates. J. Immunol. 119:1041 (1977).PubMedGoogle Scholar
  32. 32.
    Kalina, M., and G. Berke. Contact regions of cytotoxic T lymphocyte-target cell conjugates. Cell. Immunol. 25:41 (1976).PubMedCrossRefGoogle Scholar
  33. 33.
    Ryser, J.-E., Rungger-Brandle, E., Chaponnier, C., Gabbiani, G., and P. Vassalli. The area of attachment of cytotoxic T lymphocytes to their target cells shows high motility and polarization of actin, but not myosin. J. Immunol, (in press) (1982)Google Scholar
  34. 34.
    Sanderson, C.J., and A.M. Glauert. The mechanism of T cell mediated cytotoxicity. V. Morphological studies by electron microscopy. Proc. Roy. Soc. Lond., Ser. B. 198:315 (1977).CrossRefGoogle Scholar
  35. 35.
    Sanderson, C.J., and A.M. Glauert. The mechanism of T cell mediated cytotoxicity. VI. T-cell projections and their role in target cell killing. Immunology 36:119 (1979).PubMedGoogle Scholar
  36. 36.
    Barber, T.A., and B.J. Alter. Ultrastructure of effector- target cell interaction in secondary cell-mediated lympholysis. Scand. J. Immunol. 7:57 (1978).PubMedCrossRefGoogle Scholar
  37. 37.
    Biberfeld, P., and A. Johansson. Contact areas of cytotoxic lymphocytes and target cells. An electron microscopic study. Exp. Cell Res. 94:79 (1975).PubMedCrossRefGoogle Scholar
  38. 38.
    Berke, G., Hu, V., McVey, E., and W.R. Clark. T lymphocyte- mediated cytolysis. I. A common mechanism for target recognition in specific and lectin-dependent cytolysis. J. Immunol. 127:776 (1981).PubMedGoogle Scholar
  39. 39.
    Seeman, P. Ultrastructure of membrane lesions in immune lysis, osmotic lysis and drug-induced lysis. Fed. Proc. 33:216 (1974).Google Scholar
  40. 40.
    Glasebrook, A.L. Conjugate formation by primary and secondary populations of mruine immune T Ijrmphocytes. J. Immunol. 121:1870 (1978).PubMedGoogle Scholar
  41. 41.
    Shortman, K., and P. Golstein. Target cell recognition by cytolytic T cells: Different requirements for the formation of strong conjugates or for proceeding to lysis. J. Immunol. 123:833 (1979).PubMedGoogle Scholar
  42. 42.
    Grimm, E., and B. Bonavida. Mechanism of cell-mediated cyto- toxocity at the single cell level. I. Estimation of cytotoxic T lymphocyte frequency and relative lytic efficiency. J. Immunol. 123:2861 (1979).PubMedGoogle Scholar
  43. 43.
    Gately, M.K., Wechter, W.J., and E. Martz. Early steps in specific tumor cell lysis by sensitized mouse T lymphocytes. IV. Inhibition of programming for lysis by pharmacological agents. J. Immunol. 125:783 (1980).PubMedGoogle Scholar
  44. 44.
    Fox, J.E.B., and D.R. Phillips. Inhibition of actin poljmier- ization in blood platelets by cytochalasins. Nature 292:650 (1981).PubMedCrossRefGoogle Scholar
  45. 45.
    Golstein, P., Foa, C., and I.C.M. McLennan. Mechanism of T cell mediated cytolysis: the differential impact of cytochalasins at the recognition and lethal hit stages. Eur. J. Immunol. 8:302 (1978).PubMedCrossRefGoogle Scholar
  46. 46.
    Martz, E. Immune T lymphocyte to tumor cell adherion. Magnesium sufficient, calcium insufficient. J. Cell. Biol. 84:584 (1980).PubMedCrossRefGoogle Scholar
  47. 47.
    Berke, G., Fishelson, Z., and B. Schick. Hyperthermia and formaldehyde can dissociate the binding and killing activities of cytolytic T lymphocytes. Transplant. Proc. 11:804 (1979).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • J.-E. Ryser
    • 1
  • P. Vassalli
    • 1
  1. 1.Department of Pathology, Faculty of MedicineUniversity of GenevaGeneva 4Switzerland

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